Ipsen Pharmaceuticals Ltd

Somatuline LA 30mg, powder and solvent for suspension for injection

Each vial contains lanreotide 30mg as lanreotide acetate.

After reconstitution, 1 ml of the suspension contain 15mg lanreotide as lanreotide acetate

For a full list of excipients, see section 6.1.

Powder and solvent for suspension for injection.

Powder: A practically white friable cake.

Solvent: A clear colourless solution.

Acromegaly:

Somatuline LA is indicated for the treatment of acromegaly when the circulating levels of growth hormone and insulin-like growth factor remain abnormal after surgery and/or radiotherapy, or in patients who require treatment prior to such intervention.

Thyrotrophic Adenomas:

Somatuline LA is indicated for the treatment of primary thyrotrophic adenomas.

Neuroendocrine Tumours:

Somatuline LA is also indicated for the relief of symptoms associated with carcinoid tumours.

Digestive Fistulae:

Treatment of post operative , simple, externalised, pancreatic, duodenal and small intestine fistulae.

Acromegaly/ Neuroendocrine tulours/Thyrotrophic Adenomas

For intramuscular injection only.

Adults:

Initially, one injection every fourteen (14) days. The frequency of injection may be varied in accordance with the individual patient's response (as judged by symptomatology and/or biochemical monitoring). Injection sites should be varied.

Digestive fistulae

Initially, one intramuscular injection should be given to assess the patient's response.

In patients with fistulae volume drainage reduction of at least 50% after 72h, 1 injection should be given every 10 days until closure of the fistula, or up to a maximum of 3 additional injections.

Children:

The safety and efficacy of this product in children has not been established, hence the use of Somatuline LA cannot be advised.

Elderly:

Neither pharmacokinetics nor adverse event profiles appear to be altered in elderly subjects; hence no dose modification is considered necessary.

Hepatic Impairment:

In hepatically impaired patients, lanreotide kinetic parameters were not significantly altered; therefore the dosing of Somatuline LA should be adapted according to the therapeutic response as for other patients.

Renal Impairment:

In renally impaired patients, a decrease in lanreotide clearance and increase in AUC and t½ were observed and such patients should be carefully monitored with prolongation of dosing interval, if necessary.

Somatuline LA should not be prescribed during pregnancy and lactation or in patients with hypersensitivity to the peptide or related peptides.

Pharmacological studies in animals and humans show that lanreotide, like somatostatin and its analogues, inhibit secretion of insulin and glucagon. Hence, diabetic patients treated with Somatuline LA may experience a transient decrease of blood glucose levels. Blood sugar levels should be checked in order to adjust the antidiabetic treatment, if necessary.

Somatuline LA may reduce gall bladder motility and development of gallstones has been reported in approximately 13% of patients on long term lanreotide treatment. Thus, gallbladder ultrasonography is advised at the start of treatment and every six months thereafter. If gallstones do occur, they are generally asymptomatic. Symptomatic stones should be treated as medically indicated.

Somatuline LA should only be used under hospital specialist supervision, with the appropriate facilities available for diagnosis and evaluation of response.

The gastrointestinal effects of Somatuline LA may reduce the intestinal absorption of co-administered drugs. As with other somatostatin analogues, Somatuline LA may reduce the intestinal absorption of cyclosporin A. Interactions with highly plasma protein bound drugs are unlikely in view of the moderate binding of lanreotide to serum proteins (78%).

Lanreotide may reduce insulin or oral hypoglycaemic requirements in patients with diabetes mellitus.

Studies in animals showed transitory growth retardation of offspring prior to weaning. Although no teratogenic effects have been observed in animals, in the absence of clinical experience, lanreotide must not be administered to pregnant or lactating women.

Therapy with Somatuline LA is unlikely to impair the patient's ability to drive or use machinery.

The side effects of Somatuline LA reported in clinical trials are mainly local and gastrointestinal.

Local Tolerance: Moderate, transitory pain at the injection site is sometimes associated with local redness.

General Tolerance: Gastrointestinal side effects are the most common and include: diarrhoea or soft stools, abdominal pain, flatulence, anorexia, nausea and vomiting. In general, all these side effects are mild/moderate in intensity; in most cases the frequency and intensity appear to diminish or to resolve with continued therapy.

Cases of asymptomatic and symptomatic gallbladder lithiasis have been reported in patients during prolonged administration.

A precautionary statement is included in Section 4.4; Special warnings and precautions for use.

Biological Tolerance: Altered glucose regulation has been reported in healthy volunteers.

There is no human experience of overdosage. Animal data do not predict any effects other than those on insulin and glucagon secretion and the gastrointestinal system. If overdosage occurs, symptomatic management is indicated.

Like natural somatostatin, lanreotide is peptide inhibitor of a number of endocrine, neuroendocrine, exocrine and paracrine functions. It shows good affinity for peripheral somatostatin receptors (anterior pituitary and pancreatic). In contrast, its affinity for central receptors is much lower. This profile confers a good specificity of action at the level of growth hormone and digestive hormone secretion.

Lanreotide shows a much longer duration of action than natural somatostatin. In addition, its marked selectivity for the secretion of growth hormone, compared to that of insulin, makes it a suitable candidate for the treatment of acromegaly. By inhibiting the synthesis of thyroid stimulating hormone (TSH), lanreotide also normalised the thyroid function of patients with thyrotrophin-secreting adenomas. Furthermore, the inhibitory action of lanreotide on intestinal exocrine secretion, digestive hormones and cellular proliferation mechanisms is suited to the symptomatic treatment of endocrine digestive tumours, especially carcinoids.

During a randomized, double-blind clinical study involving patients with digestive fistulae, 64.8% of the patients who received one i.m.injection of lanreotide PR30 mg were responders (i.e. presented a reduction of the drainage volume of fistulae of at least 50% within 72 hours) versus 37.7% of patients treated with placebo. In this subgroup of responder patients and upon continuation of the treatment (one i.m injection every 10 days), median fistula closure time was 14 days in patients treated with lanreotide PR 30mg versus 17 days in patients treated with placebo.

The plasma profile of Somatuline LA administered intramuscularly in healthy volunteers, is characterised by an initial rapid release phase followed by a prolonged slow release phase. The first plasma peak (C_max:6.8 +3.8microgram/1) occurs at 1.4 + 0.8 hours and the second (C_max:2.5+0.9microgram/1) at 1.9 + 1.8 days. The absolute bioavailability is 46.1 + 16.7%. The mean residence time of 8.0 + 1.0 days and the apparent half-life of 5.2+2.5 days, confirm the prolonged release of the product.

After a single administration in acromegaly patients, a comparable pharmacokinetic profile is observed and the levels of growth hormone and IGF-1 are significantly reduced for a period of about 14 days. With repeated administration over several months, there is no evidence of accumulation of lanreotide.

The resorption of Somatuline LA is complete in 45-60 days.

In vitro and animal toxicity studies have not shown any specific toxic potential for lanreotide. The observed effects are related to the pharmacological properties of lanreotide on the endocrine system. In rats, reversible testicular atrophy was observed and also an increase in pre and post-implantation loss, only at the high doses level.

Powder for suspension

Lactide glycolide copolymer

Lactic glycolic copolymer

Mannitol (E421)

Carmellose sodium (E466 )

Polysorbate 80 (E433)

Solvent for suspension

Mannitol (E421)

Water for injections

This medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6.

Store at a temperature between 2 and 8ºC (in a refrigerator). Do not freeze.

Type 1, clear, slightly tinted glass vial (4 ml capacity) containing the sterile Somatuline LA;

2 ml, Type 1, clear, glass ampoule of sterile suspension vehicle;

Two sterile needles (1.20 x 40 mm)

One empty polypropylene syringe (3 ml).

The reconstitution of the Somatuline LA in the supplied solution must be performed immediately before injection, by shaking the vial, gently, 20 or 30 times, in order to obtain a homogeneous suspension with a milky appearance. This must not be mixed with other medications.

Discard any unused portion

Dispose of used needles in a designated sharps container.

Ipsen Pharmaceuticals Ltd

7 Upper Lesson Street

Dublin 4

Ireland

Trading as:

Ipsen Pharmaceuticals

PA 0869/004/001

Date of first authorisation: 15 June 1998

Date of last renewal: 15 June 2003

April 2008